In 1910, the British physicist J. J. Thomson observed that positive ions and neutral atoms were released from a solid surface when bombarded with ions. Later, in 1949, improvements in vacuum pumps and associated technologies enabled the first prototype experiments on Secondary Ion Mass Spectrometry (SIMS) to be carried out by Herzog and Viehbock at the University of Vienna in Austria. Since the earliest days, the potential for SIMS to be a very powerful analytical technique has been recognised but has not yet realised its fullest potential. In the intervening years to now, the SIMS technique has expanded to encompass many different and useful methods of material analysis, many of which are not achievable by other analytical methods. These include 2 dimensional chemical mapping or imaging, depth profiling and more recently the capability to obtain detailed chemical and compositional information from biological and bio-chemical materials. The range of probes of the material has also increased, starting from elementary ion probes, such as argon or oxygen, but now including large molecular clusters such as C60, giant gas clusters and laser ablation. Other improvements to the SIMS technique have included improved mass and spatial resolution, the possibility to measure non-ionised material removed from the sample by post ionisation, the so called Secondary Neutral Mass Spectrometry (SNMS) that permits analysis of the removed material in a mass spectrometer and the ubiquitous advances in computing technology that has led to a vast array of instrument control, data capture and analysis facilities.
Several methods of analysis in a mass spectrometer are used for SIMS. These include mass separation by using powerful electromagnets, the so called Magnetic Sector instrument, mass separation by the application of Radio Frequency (RF) electric fields, the so called Quadrupole and the Ion Trap, and the separation of masses by their arrival time at a detector, the technique known as Tine of Flight (ToF). The Time of Flight SIMS technique is particularly well suited to analysis of organic samples, because it can simultaneously detect ions from a wide mass range, allowing for a very high efficiency in detecting a large proportion of secondary ions. FIG. 1 shows a typical arrangement inside the vacuum chamber of a ToF-SIMS instrument. The sample to be analysed is mounted on a holder (1) which is introduced into a vacuum chamber (2) and secured on a motion stage (3). A primary ion beam (4) is generated by an ion source (not shown), accelerated and directed at the sample. The vacuum housing (5) that encloses the ion source is shown in part. The impact of primary ions on the sample surface causes secondary ions to be ejected from the sample and these are captured and accelerated by the extraction optics (6). These ions travel in the direction (7) to enter a time of flight analyser (not shown) and ultimately to hit an ion detector. The vacuum housing (8) for the analyser is shown in part. The time of flight analyser can be simply a flight tube, but may also contain other ion-optical components such as energy-compensating devices, focusing or alignment devices or pulsing devices.
During the latter part of the twentieth century SIMS developed largely as a technique for elemental analysis. Atomic or small molecular ion beams, made of species such as Ga+, Cs+, O2+, Ar+, were used as primary ion beams to stimulate emission of secondary ions. Such primary beams cause too much damage at the sample surface and too much fragmentation of emitted material to produce large molecular secondary ions. So, the technique was limited to elemental analysis or, at best detection of small molecular fragments. Ion beams of different species offered a range of features, suiting them to different variants of SIMS analysis. For example, a small probe size is advantageous for high spatial resolution imaging or a good beam shape is advantageous for depth profiling. Oxygen beams enhance yields of positive secondary ions, whilst caesium beams enhance negative secondary ion yields.
Around the year 2000, cluster ion beams were introduced to extend the mass range of the SIMS technique and to enable organic analysis. The earliest cluster ion primary beams were small metallic clusters produced by a liquid metal ion source (LMIS), for instance gold clusters of 2 or 3 gold atoms (N. Davies, D. E. Weibel; N P. Lockyer, P. Blenkinsopp, R. Hill, J C. Vickerman Appl. Surf. Sci. 203-204 (2003) 223-227), followed by similar sources using alternative metals such as bismuth. Such beams were able to release secondary ions of whole organic molecules and large fragments, but they cause too much damage to underlying sample to continue analysis beyond the top monolayer or so of the sample surface, when used by themselves. The first cluster beam that was routinely capable of analysing a polymer or organic sample whilst etching through its bulk was the C60 ion beam (D. Weibel, S. Wong, N. Lockyer, P. Blenkinsopp, R. Hill, J C. Vickerman, Anal. Chem. 75 (2003) 1754). C60 was found to produce higher yields of organic molecules with much reduced damage to the underlying sample. This is because, with 60 atoms in its cluster, the beam energy is dissipated only in the top few layers of the sample, releasing intact secondary ions by shaking them from the surface surrounding each impact site and leaving underlying chemistry largely undamaged.
The next significant development in ion beams for organic SIMS was the Gas Cluster Ion Beam (GCIB). Cluster formation through a supersonic expansion was first studied by Becker et al. for thermonuclear fuel applications (E. W. Becker, K. Bier, W. Henkes, Z. Phys. 146 (1956) 6511). Clusters are typically formed by creating an adiabatic expansion of a gas from a high pressure region into a low pressure region through a small orifice. As the gas expands, it cools, and clusters are formed. These clusters can range from 2 atoms up to tens of thousands of atoms. By ionising the clusters, it is possible to produce charged clusters, which can then be mass filtered if required, and accelerated to produce an ion beam that can be directed onto a sample. Cluster beams can deliver a large amount of the cluster material to the sample at relatively low energies per atom within the cluster. This has opened out new applications using them for cleaning surfaces, reducing surface roughness, and depositing material on the surface.
Over the past decade, there has been much work done with argon gas cluster ion beams for use in modifying surface properties of materials (Isao Yamada, Jiro Matsuo, Noriaki Toyoda, Norihisa Hagiwara, Nucl. Instr. and Meth. B 161-163 (2000) 980-985). More recently, argon gas cluster ion beams have been used for sputtering material in SIMS, where they have been shown to be able to sputter large organic molecules with less fragmentation and damage then occurs when atomic ion beams are used (Sadia Rabbani, Andrew M. Barber, John S. Fletcher, Nicholas P. Lockyer, and John C. Vickerman, Anal. Chem. 2011, 83, 3793-3800).
In present day organic SIMS analysis, the C60 and argon cluster beams are used as low-damage beams either for etching away layers of sample between analyses by another ion beam, or for direct SIMS analysis. The use of these cluster beams has opened out the use of SIMS in analysis of polymers and biological material. However, there is a remaining problem of sensitivity to large molecular species which may be present in very small concentrations in the sample. This problem arises from the need to detect such large molecules from within a very small area of the sample. One of the most promising fields for organic SIMS is in the imaging of cells, tissue, or other structures with very fine features. The imaging technique usually proceeds by scanning the primary ion beam across the sample in steps, thus acquiring a mass spectrum from a series of pixels. With a suitable scan pattern, a complete image of a sample area is built up, with a mass spectrum for each pixel in the image. With present day ion beams (C60 and argon clusters) detection of important organic molecules, such as lipids or peptides, becomes unsatisfactory when the pixel size decreases below a few square microns. The number of molecules available for interrogation within such a small area is limited and the technique may need to be sensitive to less than an attomole presence of a particular molecule in each pixel. ToF SIMS instrumentation has been improved to give high transmission and dynamic range in order to maximise sensitivity; there remains little room for improvement through instrument development. However, there is an opportunity to achieve significantly higher sensitivity by increasing the yield of secondary ions. Most of the material that is sputtered from the surface leaves as neutral molecules or fragments. By causing the ionisation of more of this material, sensitivity in organic analysis would be increased proportionately.
We have invented a water cluster primary ion beam that provides a surprisingly good enhancement in ion yields. Water clusters formed by adiabatic gas expansion have been previously studied for their effects on smoothing and oxidation of surfaces (Hiromichi Ryuto, Keiji Tada, Gikan, H. Takaoka, Vacuum Vol. 84, Issue 5, 10 Dec. 2009, Pages 501-504), and methods for generating such clusters have been described. Droplets of protonated water (ie. H(H2O)n+) produced by squirting a liquid mixture of water, methanol and acetic acid through a fine capillary have been found to give a small increase in ionisation when sprayed at low energy onto a surface during SIMS analysis (Guangtao Li, Jobin Cyriac, Liang Gao and R. Graham Cooks, Surface and Interface Analysis Vol. 43, Issue 1-2, 498-501, January-February 2011) compared to the significant increase in ion yield that can be achieved with the present disclosure. This experiment used a wide spray of protonated droplets rather than a focussed beam of water clusters. In our disclosure, the beam can be focused to less than 5 microns, allowing the use of the beam for analysis at high spatial resolution or for precise co-targeting of an analysis point with another beam performing analysis. Organic samples are often frozen for SIMS analysis in order to preserve the hydrated structures of the samples, for instance in analysis of cells or tissues, or to stabilise chemistry under ion bombardment, as in some multi-interface polymer analysis. A broad water cluster ion beam or a water vapour jet is undesirable for frozen samples owing to the danger of frost formation over the sample surface.